Yuen Tung Chan

• BSc (Hons) Biomedical Sciences
• Determining the effect of DNA-PK inhibition on ATR activation by, and sensitisation of, gemcitabine in ovarian cancer

Ovarian cancer is a common cause of cancer deathfrom gynaecologic tumours. Although treatments are available, the 5-year survival rate is poor. Once patients relapse from first line chemotherapy, they may be offered gemcitabine. Gemcitabine stops cells copying their DNA but can activate DNA damage response (DDR) in cells and confer resistance. The DDR is a defence mechanism that allows cells to protect themselves from naturally occurring DNA damage. To see if gemcitabine can be more effective by inhibiting repair of damage it causes, we used inhibitors of ATR and DNA-PKcs.

Inhibiting ATR made cells 3.6 times more sensitive to gemcitabine but inhibiting DNA-PKcs did not sensitise the cells to gemcitabine. Further investigation of the combination of ATR and DNA-PK inhibitors in ovarian cancer models is warranted.

Funding source: Newcastle University

Supervisor: Prof Nicola Curtin